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4. Colonization of vancomycin-resistant Enterococcus faecium in human-derived colonic epithelium: Unraveling the transcriptional dynamics of host-enterococcal interactions

Author

Stege, Paul B, primary, Beekman, Jeffrey M, additional, Hendrickx, Antoni P A, additional, van Eijk, Laura, additional, Rogers, Malbert R C, additional, Suen, Sylvia W F, additional, Vonk, Annelotte M, additional, Willems, Rob J L, additional, and Paganelli, Fernanda L, additional

Published
2024
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5. Colonization of vancomycin-resistant Enterococcus faecium in human-derived colonic epithelium: Unraveling the transcriptional dynamics of host-enterococcal interactions

Author

MMB, UMC Utrecht Holding, Longziekten onderzoek 2, Onderzoek, Child Health, Regenerative Medicine and Stem Cells, MMB Research line 2, Beleid & Communicatie, Infection & Immunity, Stege, Paul B., Beekman, Jeffrey M., Hendrickx, Antoni P.A., Van Eijk, Laura, Rogers, Malbert R.C., Suen, Sylvia W.F., Vonk, Annelotte M., Willems, Rob J.L., Paganelli, Fernanda L., MMB, UMC Utrecht Holding, Longziekten onderzoek 2, Onderzoek, Child Health, Regenerative Medicine and Stem Cells, MMB Research line 2, Beleid & Communicatie, Infection & Immunity, Stege, Paul B., Beekman, Jeffrey M., Hendrickx, Antoni P.A., Van Eijk, Laura, Rogers, Malbert R.C., Suen, Sylvia W.F., Vonk, Annelotte M., Willems, Rob J.L., and Paganelli, Fernanda L.

Published
2024

6. Gut Colonization by ESBL-Producing Escherichia coli in Dogs Is Associated with a Distinct Microbiome and Resistome Composition

Author

Stege, Paul B., primary, Hordijk, Joost, additional, Sandholt, Arnar K. S., additional, Zomer, Aldert L., additional, Viveen, Marco C., additional, Rogers, Malbert R. C., additional, Salomons, Moniek, additional, Wagenaar, Jaap A., additional, Mughini-Gras, Lapo, additional, Willems, Rob J. L., additional, and Paganelli, Fernanda L., additional

Published
2023
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7. Gut Colonization by ESBL-Producing Escherichia coli in Dogs Is Associated with a Distinct Microbiome and Resistome Composition

Author

Stege, Paul B, Hordijk, Joost, Sandholt, Arnar K S, Zomer, Aldert L, Viveen, Marco C, Rogers, Malbert R C, Salomons, Moniek, Wagenaar, Jaap A, Mughini-Gras, Lapo, Willems, Rob J L, Paganelli, Fernanda L, Stege, Paul B, Hordijk, Joost, Sandholt, Arnar K S, Zomer, Aldert L, Viveen, Marco C, Rogers, Malbert R C, Salomons, Moniek, Wagenaar, Jaap A, Mughini-Gras, Lapo, Willems, Rob J L, and Paganelli, Fernanda L

Abstract

The gut microbiome of humans and animals acts as a reservoir of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC). Dogs are known for having a high prevalence of ESBL-EC in their gut microbiota, although their ESBL-EC carrier status often shifts over time. We hypothesized that the gut microbiome composition of dogs is implicated in ESBL-EC colonization status. Therefore, we assessed whether ESBL-EC carriage in dogs is associated with changes in the gut microbiome and resistome. Fecal samples were collected longitudinally from 57 companion dogs in the Netherlands every 2 weeks for a total of 6 weeks ( n = 4 samples/dog). Carriage of ESBL-EC was determined through selective culturing and PCR and in line with previous studies, we observed a high prevalence of ESBL-EC carriage in dogs. Using 16s rRNA gene profiling we found significant associations between detected ESBL-EC carriage and an increased abundance of Clostridium sensu stricto 1, Enterococcus, Lactococcus, and the shared genera of Escherichia -Shigella in the dog microbiome. A resistome capture sequencing approach (ResCap) furthermore, revealed associations between detected ESBL-EC carriage and the increased abundance of the antimicrobial resistance genes: cmlA, dfrA, dhfR, floR, and sul3. In summary, our study showed that ESBL-EC carriage is associated with a distinct microbiome and resistome composition. IMPORTANCE The gut microbiome of humans and animals is an important source of multidrug resistant pathogens, including beta-lactamase-producing Escherichia coli (ESBL-EC). In this study, we assessed if the carriage of ESBL-EC in dogs was associated with changes in gut composition of bacteria and antimicrobial resistant genes (ARGs). Therefore, stool samples from 57 dogs were collected every 2 weeks for a total of 6 weeks. Sixty eight percent of the dogs carried ESBL-EC during at least one of the time points analyzed. By investigating the gut microbiome and resistome composition, we ob

Published
2023

8. Gut Colonization by ESBL-Producing Escherichia coli in Dogs Is Associated with a Distinct Microbiome and Resistome Composition

Author

Infectious Diseases and Immunology, IRAS OH Epidemiology Microbial Agents, Klinische infectiologie en microb. lab., IRAS – One Health Microbial, Infectious Diseases and Immunology - KLIF, Stege, Paul B, Hordijk, Joost, Sandholt, Arnar K S, Zomer, Aldert L, Viveen, Marco C, Rogers, Malbert R C, Salomons, Moniek, Wagenaar, Jaap A, Mughini-Gras, Lapo, Willems, Rob J L, Paganelli, Fernanda L, Infectious Diseases and Immunology, IRAS OH Epidemiology Microbial Agents, Klinische infectiologie en microb. lab., IRAS – One Health Microbial, Infectious Diseases and Immunology - KLIF, Stege, Paul B, Hordijk, Joost, Sandholt, Arnar K S, Zomer, Aldert L, Viveen, Marco C, Rogers, Malbert R C, Salomons, Moniek, Wagenaar, Jaap A, Mughini-Gras, Lapo, Willems, Rob J L, and Paganelli, Fernanda L

Published
2023

9. Gut Colonization by ESBL-Producing Escherichia coli in Dogs Is Associated with a Distinct Microbiome and Resistome Composition

Author

MMB RZN, Infection & Immunity, MMB Research line 2, Stege, Paul B., Hordijk, Joost, Sandholt, Arnar K.S., Zomer, Aldert L., Viveen, Marco C., Rogers, Malbert R.C., Salomons, Moniek, Wagenaar, Jaap A., Mughini-Gras, Lapo, Willems, Rob J.L., Paganelli, Fernanda L., MMB RZN, Infection & Immunity, MMB Research line 2, Stege, Paul B., Hordijk, Joost, Sandholt, Arnar K.S., Zomer, Aldert L., Viveen, Marco C., Rogers, Malbert R.C., Salomons, Moniek, Wagenaar, Jaap A., Mughini-Gras, Lapo, Willems, Rob J.L., and Paganelli, Fernanda L.

Published
2023

12. Species-Specific Patterns of Gut Metabolic Modules in Dutch Individuals with Different Dietary Habits

Author

MMB Research line 2, Infection & Immunity, Shetty, Sudarshan A., Stege, Paul B., Hordijk, Joost, Gijsbers, Esther, Dierikx, Cindy M., Van Duijkeren, Engeline, Franz, Eelco, Willems, Rob J.L., Paganelli, Fernanda L., Fuentes, Susana, MMB Research line 2, Infection & Immunity, Shetty, Sudarshan A., Stege, Paul B., Hordijk, Joost, Gijsbers, Esther, Dierikx, Cindy M., Van Duijkeren, Engeline, Franz, Eelco, Willems, Rob J.L., Paganelli, Fernanda L., and Fuentes, Susana

Published
2022

13. Impact of long-term dietary habits on the human gut resistome in the Dutch population

Author

MMB Research line 2, Infection & Immunity, MMB Zorg, Stege, Paul B., Hordijk, Joost, Shetty, Sudarshan A., Visser, Michael, Viveen, Marco C., Rogers, Malbert R.C., Gijsbers, Esther, Dierikx, Cindy M., van der Plaats, Rozemarijn Q.J., van Duijkeren, Engeline, Franz, Eelco, Willems, Rob J.L., Fuentes, Susana, Paganelli, Fernanda L., MMB Research line 2, Infection & Immunity, MMB Zorg, Stege, Paul B., Hordijk, Joost, Shetty, Sudarshan A., Visser, Michael, Viveen, Marco C., Rogers, Malbert R.C., Gijsbers, Esther, Dierikx, Cindy M., van der Plaats, Rozemarijn Q.J., van Duijkeren, Engeline, Franz, Eelco, Willems, Rob J.L., Fuentes, Susana, and Paganelli, Fernanda L.

Published
2022

14. Ablation of liver Fxr results in an increased colonic mucus barrier in mice.

Author

dI&I I&I-2, Dep Biomolecular Health Sciences, Pathobiologie, dPB RMSC, Ijssennagger, Noortje, van Rooijen, Kristel S., Magnúsdóttir, Stefanía, Ramos Pittol, José M., Willemsen, Ellen C.L., de Zoete, Marcel R., Baars, Matthijs J.D., Stege, Paul B., Colliva, Carolina, Pellicciari, Roberto, Youssef, Sameh A., de Bruin, Alain, Vercoulen, Yvonne, Kuipers, Folkert, van Mil, Saskia W.C., dI&I I&I-2, Dep Biomolecular Health Sciences, Pathobiologie, dPB RMSC, Ijssennagger, Noortje, van Rooijen, Kristel S., Magnúsdóttir, Stefanía, Ramos Pittol, José M., Willemsen, Ellen C.L., de Zoete, Marcel R., Baars, Matthijs J.D., Stege, Paul B., Colliva, Carolina, Pellicciari, Roberto, Youssef, Sameh A., de Bruin, Alain, Vercoulen, Yvonne, Kuipers, Folkert, and van Mil, Saskia W.C.

Published
2021

15. Ablation of liver Fxr results in an increased colonic mucus barrier in mice

Author

CMM Groep Van Mil, Cancer, DBG Metabole en Endocriene Ziekten, MMB Research line 2, Infection & Immunity, CMM Groep Vercoulen, CMM, Child Health, Ijssennagger, Noortje, van Rooijen, Kristel S., Magnúsdóttir, Stefanía, Ramos Pittol, José M., Willemsen, Ellen C.L., de Zoete, Marcel R., Baars, Matthijs J.D., Stege, Paul B., Colliva, Carolina, Pellicciari, Roberto, Youssef, Sameh A., de Bruin, Alain, Vercoulen, Yvonne, Kuipers, Folkert, van Mil, Saskia W.C., CMM Groep Van Mil, Cancer, DBG Metabole en Endocriene Ziekten, MMB Research line 2, Infection & Immunity, CMM Groep Vercoulen, CMM, Child Health, Ijssennagger, Noortje, van Rooijen, Kristel S., Magnúsdóttir, Stefanía, Ramos Pittol, José M., Willemsen, Ellen C.L., de Zoete, Marcel R., Baars, Matthijs J.D., Stege, Paul B., Colliva, Carolina, Pellicciari, Roberto, Youssef, Sameh A., de Bruin, Alain, Vercoulen, Yvonne, Kuipers, Folkert, and van Mil, Saskia W.C.

Published
2021

16. Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli

Author

Pleguezuelos-Manzano, Cayetano, Puschhof, Jens, Rosendahl Huber, Axel, van Hoeck, Arne, Wood, Henry M, Nomburg, Jason, Gurjao, Carino, Manders, Freek, Dalmasso, Guillaume, Stege, Paul B, Paganelli, Fernanda L, Geurts, Maarten H, Beumer, Joep, Mizutani, Tomohiro, Miao, Yi, van der Linden, Reinier, van der Elst, Stefan, Garcia, K Christopher, Top, Janetta, Willems, Rob J L, Giannakis, Marios, Bonnet, Richard, Quirke, Phil, Meyerson, Matthew, Cuppen, Edwin, van Boxtel, Ruben, Clevers, Hans, Pleguezuelos-Manzano, Cayetano, Puschhof, Jens, Rosendahl Huber, Axel, van Hoeck, Arne, Wood, Henry M, Nomburg, Jason, Gurjao, Carino, Manders, Freek, Dalmasso, Guillaume, Stege, Paul B, Paganelli, Fernanda L, Geurts, Maarten H, Beumer, Joep, Mizutani, Tomohiro, Miao, Yi, van der Linden, Reinier, van der Elst, Stefan, Garcia, K Christopher, Top, Janetta, Willems, Rob J L, Giannakis, Marios, Bonnet, Richard, Quirke, Phil, Meyerson, Matthew, Cuppen, Edwin, van Boxtel, Ruben, and Clevers, Hans

Abstract

Various species of the intestinal microbiota have been associated with the development of colorectal cancer1,2, but it has not been demonstrated that bacteria have a direct role in the occurrence of oncogenic mutations. Escherichia coli can carry the pathogenicity island pks, which encodes a set of enzymes that synthesize colibactin3. This compound is believed to alkylate DNA on adenine residues4,5 and induces double-strand breaks in cultured cells3. Here we expose human intestinal organoids to genotoxic pks+ E. coli by repeated luminal injection over five months. Whole-genome sequencing of clonal organoids before and after this exposure revealed a distinct mutational signature that was absent from organoids injected with isogenic pks-mutant bacteria. The same mutational signature was detected in a subset of 5,876 human cancer genomes from two independent cohorts, predominantly in colorectal cancer. Our study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.

Published
2020

20. CRISPR-Cas9-mediated genome editing in vancomycin-resistant Enterococcus faecium

Author

MMB Research line 2, Infection & Immunity, de Maat, Vincent, Stege, Paul B., Dedden, Mark, Hamer, Maud, van Pijkeren, Jan Peter, Willems, Rob J.L., van Schaik, Willem, MMB Research line 2, Infection & Immunity, de Maat, Vincent, Stege, Paul B., Dedden, Mark, Hamer, Maud, van Pijkeren, Jan Peter, Willems, Rob J.L., and van Schaik, Willem

Published
2019

21. Mutational signature in colorectal cancer caused by genotoxic pks+E. coli.

Author

Pleguezuelos-Manzano, Cayetano, Puschhof, Jens, Rosendahl Huber, Axel, van Hoeck, Arne, Wood, Henry M., Nomburg, Jason, Gurjao, Carino, Manders, Freek, Dalmasso, Guillaume, Stege, Paul B., Paganelli, Fernanda L., Geurts, Maarten H., Beumer, Joep, Mizutani, Tomohiro, Miao, Yi, van der Linden, Reinier, van der Elst, Stefan, Genomics England Research Consortium, Ambrose, J. C., and Arumugam, P.

Abstract

Various species of the intestinal microbiota have been associated with the development of colorectal cancer1,2, but it has not been demonstrated that bacteria have a direct role in the occurrence of oncogenic mutations. Escherichia coli can carry the pathogenicity island pks, which encodes a set of enzymes that synthesize colibactin3. This compound is believed to alkylate DNA on adenine residues4,5 and induces double-strand breaks in cultured cells3. Here we expose human intestinal organoids to genotoxic pks+E. coli by repeated luminal injection over five months. Whole-genome sequencing of clonal organoids before and after this exposure revealed a distinct mutational signature that was absent from organoids injected with isogenic pks-mutant bacteria. The same mutational signature was detected in a subset of 5,876 human cancer genomes from two independent cohorts, predominantly in colorectal cancer. Our study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island. Organoids derived from human intestinal cells that are co-cultured with bacteria carrying the genotoxic pks+ island develop a distinct mutational signature associated with colorectal cancer. [ABSTRACT FROM AUTHOR]

Published
2020
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22. Mutational signature in colorectal cancer caused by genotoxic pks + E. coli.

Author

Pleguezuelos-Manzano C, Puschhof J, Rosendahl Huber A, van Hoeck A, Wood HM, Nomburg J, Gurjao C, Manders F, Dalmasso G, Stege PB, Paganelli FL, Geurts MH, Beumer J, Mizutani T, Miao Y, van der Linden R, van der Elst S, Garcia KC, Top J, Willems RJL, Giannakis M, Bonnet R, Quirke P, Meyerson M, Cuppen E, van Boxtel R, and Clevers H

Subjects
Coculture Techniques, Cohort Studies, Consensus Sequence, DNA Damage, Gastrointestinal Microbiome, Humans, Organoids cytology, Organoids metabolism, Organoids microbiology, Peptides genetics, Polyketides, Colorectal Neoplasms genetics, Colorectal Neoplasms microbiology, Escherichia coli genetics, Escherichia coli pathogenicity, Genomic Islands genetics, Mutagenesis, Mutation
Abstract

Various species of the intestinal microbiota have been associated with the development of colorectal cancer 1,2 , but it has not been demonstrated that bacteria have a direct role in the occurrence of oncogenic mutations. Escherichia coli can carry the pathogenicity island pks, which encodes a set of enzymes that synthesize colibactin 3 . This compound is believed to alkylate DNA on adenine residues 4,5 and induces double-strand breaks in cultured cells 3 . Here we expose human intestinal organoids to genotoxic pks + E. coli by repeated luminal injection over five months. Whole-genome sequencing of clonal organoids before and after this exposure revealed a distinct mutational signature that was absent from organoids injected with isogenic pks-mutant bacteria. The same mutational signature was detected in a subset of 5,876 human cancer genomes from two independent cohorts, predominantly in colorectal cancer. Our study describes a distinct mutational signature in colorectal cancer and implies that the underlying mutational process results directly from past exposure to bacteria carrying the colibactin-producing pks pathogenicity island.

Published
2020
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